CN1460723A - 具有亲水和疏水区域的生物分子芯片平板制备方法 - Google Patents
具有亲水和疏水区域的生物分子芯片平板制备方法 Download PDFInfo
- Publication number
- CN1460723A CN1460723A CN03131473A CN03131473A CN1460723A CN 1460723 A CN1460723 A CN 1460723A CN 03131473 A CN03131473 A CN 03131473A CN 03131473 A CN03131473 A CN 03131473A CN 1460723 A CN1460723 A CN 1460723A
- Authority
- CN
- China
- Prior art keywords
- hydrophilic
- hydrophobic
- biomolecules
- binding site
- layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00427—Means for dispensing and evacuation of reagents using masks
- B01J2219/00432—Photolithographic masks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00585—Parallel processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/0061—The surface being organic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00614—Delimitation of the attachment areas
- B01J2219/00617—Delimitation of the attachment areas by chemical means
- B01J2219/00619—Delimitation of the attachment areas by chemical means using hydrophilic or hydrophobic regions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00623—Immobilisation or binding
- B01J2219/00626—Covalent
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00632—Introduction of reactive groups to the surface
- B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00725—Peptides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00731—Saccharides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/12—Specific details about manufacturing devices
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/12—Libraries containing saccharides or polysaccharides, or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
Abstract
一种制备生物分子芯片平板的方法和一种使用该芯片平板制备生物芯片的方法。芯片平板制备方法包括(a)用疏水材料涂覆载体表面形成疏水层;(b)通过放在疏水层上面的蚀刻掩膜,蚀刻疏水层,形成亲水结合位点;(c)移去剩余的蚀刻掩膜;和(d)处理其它疏水层区,恢复最初的疏水特性。生物芯片制备方法包括处理上述方法制备的芯片平板亲水结合位点表面,将包含生物分子的溶液涂布到亲水结合位点表面。
Description
发明背景
1.发明领域
本发明涉及一种基于半导体制造方法的亲水和疏水区域芯片平板的制备方法,以及一种将生物分子固定在芯片平板上制备生物芯片的方法。
2.相关技术描述
包括亲水和疏水区域核酸芯片平板的常规制备方法公开在Brennan的美国专利(6,210,894)中。按照该方法,用压电泵(piezoelectric pump)分散的反应液体微滴,利用亲水和疏水区域间表面张力差异,可以在芯片平板上分离的结合位点间转移。
特别地,如图1所示,制造核酸芯片平板的常规方法包括:(a)正性或负性光刻胶(photoresist)涂覆载体表面,随后曝光、显影形成第一次暴露的区域;(b)第一次暴露区域与氟烷基硅烷反应,从而在第一次显露区域上形成稳定的氟烷基硅烷疏水基质;(c)除去残留的光刻胶,形成第二次暴露区域;(d)第二次暴露区域与羟基或氨基烷基硅烷反应,形成功能化亲水结合位点区域。
或者,如图2所示,核酸芯片平板由下列步骤制造:(a)载体表面与羟基或氨基烷基硅烷反应,形成功能化亲水载体表面;(b)步骤(a)载体表面与临时光敏保护试剂O-硝基苄基羰基氯反应,得到光封闭(photoblocked)的载体表面;(c)通过掩膜(mask)对步骤(b)光封闭的载体表面曝光,在载体表面上形成带有未封闭羟基或氨基硅烷的未封闭区域;(d)步骤(c)的暴露表面与全氟代烷羰基卤或全氟代烷基磺酰卤反应,形成稳定的疏水区(全氟代酰基或全氟代磺酰氨基)烷基硅氧烷基质;(e)暴露其他光封闭载体表面形成未封闭羟基或氨基硅烷的图案区域(patterned region),作为功能化亲水结合位点区。
但是,这些制备核酸芯片的方法,在实际应用中很难控制几十埃的分子层厚度,分子层的作用力很弱。由于分子层薄而透明,用喷嘴涂布(applying)样品时,很难分辨分子层的亲水和疏水区域。也很难用检测体系进行自动模式检测。并且,分子层由不同于制造半导体装置的常规材料形成,很难按照一般半导体制造的方法建立校正基准来用于这种分子层的曝光。
发明概述
本发明提供了一种制备生物分子芯片平板的方法,该平板包括明显的亲水和疏水区域;该方法基于常规的半导体制造方法,很容易控制薄材料层的厚度。
本发明提供了一种用上述方法制备的生物分子芯片平板、以高精确性和高效率制造生物芯片的方法。
一方面,本发明提供了一种制造生物分子芯片平板的方法,方法包括:(a)用疏水材料涂覆载体表面形成疏水层;(b)通过放置在上面的蚀刻掩膜(etchmask),蚀刻疏水层形成亲水结合位点;(c)移去残留的蚀刻掩膜;(d)处理疏水层其他区域,恢复初始疏水性。
另一个方面,本发明提供了一种制造生物芯片的方法,包括:处理上述方法制造的芯片平板亲水结合位点表面,将包含生物分子液体涂布到亲水结合位点表面。
附图简要说明
通过详细描述典型技术方案及其附图,本发明的上面和其他的特征和优点将变得更为清晰。
图1和2例举说明制备核苷酸芯片平板的常规方法;
图3例举说明生物分子芯片平板的结构,以及一种按照本发明技术方案制备平板的方法;
图4例举说明,喷点在芯片平板疏水性区域的生物分子液滴,由于表面张力迁移到亲水区域。
发明详述
本发明提供了制造生物分子芯片平板的方法以及用芯片平板制备生物芯片方法的技术方案。
参照图3,按照本发明的技术方案,制造生物分子芯片平板的方法,包括用疏水材料涂覆载体1表面,形成疏水层3(步骤(a))。接着,疏水层3通过在其上面的蚀刻掩膜,蚀刻形成亲水结合位点6(步骤(b))。移去使用的蚀刻掩膜(步骤(c)),处理疏水层其他区域,恢复初始的疏水特性(步骤(d))。
步骤(a)中,可用作载体的合适材料,包括,但不限于,玻璃、石英、硅、陶瓷、塑料、金属等。任何能成膜且具疏水性质的材料,可用来形成疏水层。这些疏水材料实例包括,例如,碳氟聚合物,如聚四氟乙烯、氟化聚亚胺、氟化聚丙烯酸酯、氟化聚醚等;聚烃类,如聚苯乙烯、聚乙烯及其衍生物、聚降冰片烯及其衍生物等。聚酯,如聚对苯二甲酸乙二醇酯(polyethyleneterephthalate,PET)等;钻石类(diamond-like)碳等。
步骤(a)用疏水材料进行涂覆,可用相关领域的广为熟知的方法进行,例如,螺旋涂覆(spin coating)、等离子体增强化学蒸气沉积(plasma enhancedchemical vapour deposition,PECVD)、形成自组装单层的方法、蒸发、浸渍(dipping)等。得到的疏水层3具有,但不限于,几十埃到几微米的厚度。疏水层3形成以后,在100-200℃进行软烘烤(soft baking)和硬烘烤(hardbaking)1-30分钟除去溶剂以对疏水层进行脱气。疏水性层形成后,以等离子态氩气(Ar)或氧气(O2)活化,随后用光刻胶或另一种金属掩膜材料螺旋涂覆。
本发明的制造生物分子芯片平板方法,进一步包括,步骤(a)涂覆疏水层前,在载体1表面形成亲水层2,如图3所示。亲水层2可为天然的氧化物层。这种亲水层,包括天然氧化物层,由,例如,SiO2,Al2O3,SiON,氮化铝,聚甲基丙烯酸甲酯(PMMA),聚丙烯酸甲酯(PMA),聚乙烯醇(polyvinylalcohol,PVA)、聚羟基苯乙烯、聚乙腈、聚丙烯酸或聚四氢呋喃形成。亲水层2可用,例如,螺旋涂覆、热湿氧化(thermal wet oxidation),热干氧化(thermaldry oxidation)、等离子体增强化学蒸气沉积(PECVD)或其他方法形成。
按照本发明,步骤(b)中,步骤(a)形成的疏水层3用掩膜材料覆盖,随后曝光、显影(development)、图案化(patterning)形成流水性层3的蚀刻掩膜4′,该蚀刻掩膜4′暴露了疏水层3的一个区域,此区域会在制备完成的平板芯片中作为亲水区域,也就是结合位点5。蚀刻掩膜由,例如,包含负性或正性光刻胶的光敏聚合物、金属硬质掩膜材料、SiO2、多晶硅(polysilicon)或氮化硅。亲水区域为相对于疏水区域的凹陷或隆起,取决于需要形成结合位点的种类。
步骤(b)中,通过蚀刻掩膜4’暴露的疏水层区,蚀刻形成亲水结合位点5。蚀刻可用干蚀刻(dry etching)或湿蚀刻(wet etching)。湿蚀刻时,带有疏水层3的载体1浸没在蚀刻剂(etchant)中,离解疏水层3的暴露区,暴露亲水结合位点5。合适蚀刻剂的实例包括,但不限于,H2SO4、H3PO4、H2O2、HF、HCl和NH4OH。干蚀刻主要用等离子体气体经反应离子蚀刻(reactive ion etching,RIE),成灰等过程,直至显露出亲水结合位点5。合适蚀刻气体的实例包括,但不限于,O2,Ar,SF6,CF4,BCl3,Cl2,和SiCl2,其中优选O2或Ar。
步骤(c)中,移去步骤(b)蚀刻后保留的蚀刻掩膜4,暴露疏水性区6。在进行如RIE的干蚀刻或用化学试剂的湿蚀刻时,光刻胶蚀刻掩膜4’部分移去。但是,当光刻胶蚀刻掩膜4太厚或蚀刻率低,即使疏水层3蚀刻完成后,蚀刻掩膜仍然保留,例如,氟碳聚合物形成的疏水性层。用光刻胶剥离剂,如H2SO4,H2O2,丙酮等移去残留的蚀刻掩膜4。或者,蚀刻掩膜4也可通过延长疏水层3的蚀刻时间除去,这样光刻胶蚀刻掩膜以及疏水层3的显露部分可以完全地除去。当使用金属硬质掩膜时,可用合适的蚀刻技术来移去掩膜。
按照本发明,步骤(d)中,疏水区域7的初始疏水性得到恢复。通常,由,例如,碳氟聚合物、聚烃类等形成的疏水层,在进行Ar活化、蚀刻和蚀刻掩膜去除过程中,失去了部分疏水性。例如,疏水性层的水接触角减少到约50度。步骤(d)中,失去的亲水层的初始疏水性,例如,通过热处理得到恢复。热处理在等于或高于疏水层3被涂覆后进行的烘烤温度(例如100-200℃)下进行1-30分钟。结果,疏水层3疏水性得到恢复,例如,水接触角为105度。优选最终疏水性区7的表面水接触角为105度或更高,表面能为约20达因/厘米或更低。并且,优选最终亲水性区6表面水接触角为105度或更低。
依照本发明,制备生物芯片的方法包括:用依照本发明上面描述的方法制备芯片平板;处理芯片平板亲水性结合位点表面;包含生物分子的溶液涂布到亲水结合位点表面。亲水结合位点表面,用能提高生物分子与亲水结合位点亲和力的化合物处理。例如,亲水结合位点表面可用氨基丙基三乙氧基硅烷处理,将氨基连接到亲水结合位点表面。任何类型的生物分子,包括核酸,蛋白质,酶底物,辅酶(cofactor),配体和多糖等可配成溶液,涂布到亲水结合位点上。这些生物分子可单独或与其他化合物结合使用,溶解在合适的溶剂中后使用。凝胶基质-DNA复合物溶液优选作为亲水结合位点的溶液。凝胶基质-DNA复合物可用下列方法制备,例如,寡核苷酸共价结合到凝胶基质上,后者通过带有环氧基团的聚乙二醇(PEG)衍生物和交联剂,如分子量为10,000或更低的聚乙二醇二胺偶合反应。这里使用的凝胶基质为三维凝胶基质,优选由在2个或更多方向有聚乙二醇分支的PEG衍生物与交联剂交联制备。PEG衍生物包括由乙氧化季戊四醇与表氯醇反应形成的PEG衍生物,在韩国专利申请(No.10-2001-53687)中公开了。包含生物分子的溶液通过喷或点,例如,用压电泵,以微滴涂布到亲水结合位点。或者可以将含亲水结合位点的芯片平板浸渍(dipping)到生物分子溶液中。涂布到亲水结合位点的溶液中的生物分子以共价或非共价结合到芯片平板的亲水结合位点。如果生物分子是亲水的,即使生物分子喷点在疏水区,它们会由于表面张力迁移到亲水性结合位点。
依照本发明,制备生物芯片中,包含生物分子的溶液可以涂布到多张芯片或经切割形成的单张芯片的载体上。切割时,多张芯片载体上表面可用聚合物膜或UV带覆盖以保护亲水结合位点,避免在切割中受灰尘污染,然后撤除保护。
依照本发明,制备生物芯片的方法进一步包括,在将含生物分子溶液涂布到疏水性结合位点前,用磁性材料涂覆芯片平板亲水和疏水区的反面,以准确地将溶液涂布到期望的疏水结合位点。或者,该步涂覆磁性材料也可在载体1上形成疏水性层3(在芯片平板制备步骤(a)中)后进行。在涂布上述包含生物分子溶液之前,磁性材料可以涂覆到多张芯片载体或经切割形成的单张芯片上。涂覆磁性材料为将生物分子准确地固定在期望的结合位点上提供了校正基准。
依照本发明,尽管芯片平板生物分子结合位点如上所述为亲水性,具有疏水性结合位点和亲水性基质的芯片平板可用本发明上述方法制备。疏水性生物分子包括,例如,细胞膜蛋白、脂蛋白等。
本发明将参考下列实施例进行更详细的描述。下列实施例用于例举说明发目的,不作为发明范围的限制。
实施例1:生物分子芯片平板的制备
1.用碳氟聚合物形成疏水层
在带有0.05μm SiO2层的载体(0.5-mm的薄片(wafer))上,螺旋涂覆疏水性材料CytopTM(无定形碳氟,Asahi Glass Inc.,Japan)形成疏水层。在500rpm条件下,螺旋涂覆10秒,暂停20秒,2000rpm涂覆20秒。疏水层100℃软烘烤1分钟,120℃硬烘烤10分钟。碳氟聚合物形成疏水层的厚度为0.2-0.3μm。
接着,碳氟聚合物层表面用Ar活化,随后在上面进行光刻胶螺旋涂覆。在Ar气流速100sccm,压力0.24torr,RF功率100W下进行30秒激活处理。激活处理前后,测量静态水接触角、表面能以及折射指数,来判断疏水性。结果见下表1。
2.光刻胶涂覆和图案化(patterning)
活化的碳氟聚合物层表面,用光刻胶AZ1512TM(Clariant,USA)螺旋涂覆,接着100℃软烘烤1分钟。在500rpm下螺旋涂覆10秒,暂停20秒,2000rpm涂覆20秒。得到的光刻胶层的厚度约为1.2μm。12W光源曝光5秒、溶液(包含6∶1的显影剂(developer)和水)中显影(development)60秒,光刻胶层形成蚀刻掩膜的图案。接着,120℃硬烘烤2分钟。
3.碳氟聚合层的蚀刻
碳氟聚合层疏水层通过蚀刻掩膜在O2气流速100sccm、压力0.2torr、功率200W下,用反应离子蚀刻(RIE)方法蚀刻30秒,暴露亲水区域。
4.光刻胶的去除
用H2SO4和H2O2(体积比4∶1)混合溶液作为蚀刻剂,120℃处理1分钟,剥离碳氟聚合层上的光刻胶蚀刻掩膜,暴露疏水区。
5.疏水特性恢复
除去光刻胶后暴露的疏水性区,进行热处理恢复初始的疏水性特性。150℃热处理5分钟,缓慢冷却。测量疏水区的静态水接触角、表面能和折射率来判断疏水性。
表1.碳氟聚合物层处理后表面特性的变化
处理类型 | 表面特性 | ||
静态水接触角(度) | 表面能(达因/厘米) | 折射率 | |
活化前 | 110 | 16.7 | 1.35 |
活化后 | 50.1 | 50.1 | 1.37 |
热处理后 | 105 | 20.2 | 1.35 |
如表1所示,用Ar活化处理后,疏水的碳氟聚合物层部分地失去了疏水特性。但是,明显地,疏水层的疏水特性在热处理后得到恢复,接近活化前的初始水平。
由于生物分子芯片平板是用半导体装置制备中使用的已知涂覆技术制备,很容易控制疏水性层厚度,使之达到均一。从上述实例可以明显看到,本发明的生物分子芯片平板,可用半导体制造方法高产率、高精确地制备。
实施例2:生物分子芯片平板的制备
生物分子芯片平板用类似于实施例1的方法制备,只是改用PECVD涂覆碳氟聚合物,而不是实施例1步骤1中的旋转涂覆方法。PECVD在Ar流速为6sccm、C4F8流速为4sccm、压力为0.6torr、功率30W的条件下进行6分钟。在PECVD过程中,载体温度保持在75℃。得到的疏水碳氟聚合物的厚度为0.2-0.3μm。
结果证实:热处理恢复了芯片平板疏水性区的最初疏水特性。由于生物分子芯片平板是用半导体装置制备中使用的已知涂覆技术来进行制备,很容易控制疏水性层厚度的均一性。从本实施例可以明显看到,依照本发明,生物分子芯片平板可用半导体制造方法高产率、高精确地制备。
实施例3:DNA芯片的制备
DNA芯片通过将DNA分子(SEQ ID No.1)固定到实施例1和2制备的、具有亲水和疏水区载体的芯片平板上来制备。DNA分子通过凝胶基质-DNA分子(合成参照韩国专利申请号10-2001-53687),固定到芯片平板上。
1.带有环氧基团PEG衍生物的合成
7.5mL表氯醇和0.32g溴化四丁铵加到2mL的NaOH溶液中(50%,按重量计算),搅拌,1g乙氧化季戊四醇缓慢加到混合液中,室温搅拌18小时。用薄层色谱监测反应完成。当反应未完成,混合物继续在60℃搅拌1小时。接着,反应物中加入30mL水稀释,用40mL二氯甲烷萃取三次。有机层用40mL饱和NaHCO3洗三次,加入无水MgSO4,减压除去溶剂。然后,得到的产物真空干燥2天,以除去残留的表氯醇。得到的带有环氧基团PEG衍生物用H-NMR鉴定,环氧基用0.1N HBr/冰醋酸滴定。
2.二胺交联剂的合成
5g(9.2mmol)的五(乙二醇)二甲苯磺酸酯溶解在40mL的DMF中,依次加入4.2g(64.1mmol)的NaN3和0.5mL吡啶,溶液140℃搅拌18小时。减压除去溶剂后,得到的产物中搅拌加入200mL水,用100mL二氯甲烷萃取。有机层用100mL盐水洗三次,加入无水MgSO4,减压除去溶剂。接着,得到的产物进行快速柱层析(EA∶nHex=1∶2)分离出二叠氮化物(diazide)中间产品。中间产品溶解在30mL甲醇中,加入10%Pd-C(0.1当量),用氢气还原18小时。用硅藻土(Celite)垫除去催化剂,乙醇洗涤硅藻土(Celite)垫。滤液和洗涤的乙醇混合,减压除去溶剂,得到二胺交联剂。
3.凝胶基质-DNA溶液的配制
1中制备的100mg的带有环氧基团的PEG衍生物中,搅拌加入4mL水。2中合成的5.8mg二胺交联剂加到混合物中,室温搅拌18小时,以液态4℃保存。
接着,向得到的凝胶基质溶液中,加入寡核苷酸(SEQ ID NO:1),37℃搅拌,放置14小时得到凝胶基质-DNA复合物的点样液。
4.喷点凝胶基质-DNA复合物溶液,制备生物芯片
首先,每块芯片平板亲水的结合位点表面用氨丙基乙氧硅烷处理,在表面上形成氨基。接着,凝胶基质-DNA复合物溶液喷点到氨丙基硅烷化结合位点,芯片板在湿箱中37℃保温4小时。为避免靶核酸固定到玻璃表面上不必要的部位,还要进行其他反应使载体上非点样位置的氨基带负电,该步是控制背景噪音的关键步骤,制备的生物芯片保存在干燥器中。
结果是,实施例中制备的96张DNA芯片中,90张评定为“好”芯片,6张评定为“坏”芯片。6张坏芯片是在喷点基质-DNA复合物溶液中,由喷嘴意外的缺陷或阻塞引起,与制备技术没有直接关系。依照本发明,当基质-DNA复合物溶液点到芯片上所有的亲水结合位点,DNA芯片就评定为“好”芯片。制备产率和精确性都很高。
依照本发明,具有亲水和疏水区的生物分子芯片平板,可以有效地用半导体制造方法来制备。
依照本发明,热处理可以用来恢复芯片制造中退化的疏水区疏水特性,这样制备的生物分子芯片平板具有分明的亲水和疏水区。
依照本发明,固定生物分子的生物芯片,可以用具有高分辨的亲水和疏水区的芯片平板、高产率和高精确地来制备。
尽管本发明参考典型的技术方案已经进行了特别说明和描述,本领域普通技术人员应该理解,可以有形式和细节上的变化,但不偏离下列权利要求限定的发明实质和范围。
序列表<110>三星电子株式会社(SAMSUNG ELECTRONICS CO.,LTD.)<120>具有亲水和疏水区域的生物分子芯片平板制备方法<160>1<170>KopatentIn 1.71<210>1<211>15<212>DNA<213>人工序列<220><223>人工聚核苷酸<400>1tgaactttgg acttc 15
Claims (17)
1.一种制备生物分子芯片平板的方法,方法包括:
(a)用疏水材料涂覆载体表面形成疏水层;
(b)通过放置在疏水层上面的蚀刻掩膜,蚀刻疏水层,形成亲水结合位点;
(c)移去残留蚀刻膜;并且
(d)处理疏水层其它区域,恢复初始的疏水性;
2.权利要求1的方法,进一步包括步骤(a)以前在载体表面形成亲水层;
3.权利要求1的方法,其中载体由玻璃、石英、硅、陶瓷、塑料或金属形成;
4.权利要求1的方法,进一步包括步骤(a)以前或步骤(d)以后,用磁化材料涂覆疏水层的载体反面。
5.权利要求1的方法,其中疏水材料选自聚四氟乙烯、氟化聚亚胺、氟化聚丙烯酸酯、氟化聚醚、聚苯乙烯、聚乙烯、聚降冰片烯和聚对苯二甲酸乙二醇酯。
6.权利要求1的方法,其中步骤(a)中载体表面疏水材料涂覆,用螺旋涂覆、等离子体增强化学蒸气沉积、形成自组装单层的方法、蒸发、浸渍进行。
7.权利要求2的方法,其中亲水层是天然氧化物层或由选自SiO2、Al2O3、SiON、氮化铝、聚甲基丙烯酸甲酯、聚丙烯酸甲酯、聚乙烯醇类、聚羟基苯乙烯、聚乙腈、聚丙烯酸或聚四氢呋喃的材料形成。
8.权利要求2的方法,其中亲水层用螺旋涂覆、等离子体增强化学蒸气沉积、形成自组装单层的方法、蒸发、浸渍进行。
9.权利要求2的方法,其中步骤(b)包括用光敏聚合物、金属硬质掩膜材料、SiO2、多晶硅或氮化硅,通过光刻形成蚀刻掩膜。
10.权利要求9的方法,其中光敏聚合物为光刻胶。
11.权利要求1的方法,其中步骤(b)蚀刻疏水层用干蚀刻或湿蚀刻进行。
12.权利要求1的方法,其中步骤(d)100-200℃加热1-30分钟。
13.一种制备生物芯片的方法,包括:
处理权利要求1方法制备的芯片平板亲水结合位点表面;及
将包含生物分子的溶液涂布到亲水结合位点表面。
14.权利要求13的方法,其中溶液中的生物分子包括核酸、蛋白质或多糖。
15.权利要求13的方法,其中包含生物分子的溶液用喷、点或浸渍的方式涂布。
16.权利要求13的方法,其中溶液中的生物分子与亲水结合位点通过化学反应形成共价或非共价键。
17.权利要求13的方法,其中亲水结合位点表面处理成带氨基表面,包含生物分子的溶液为凝胶基质-DNA复合物,后者由DNA共价结合到凝胶基质上,该凝胶基质由带有2或多个方向聚乙二醇(PEG)分支的聚乙二醇衍生物与交联剂反应得到。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR26730/02 | 2002-05-15 | ||
KR26730/2002 | 2002-05-15 | ||
KR10-2002-0026730A KR100455293B1 (ko) | 2002-05-15 | 2002-05-15 | 친수성 영역과 소수성 영역으로 구성되는 생물분자용어레이 판의 제조방법 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1460723A true CN1460723A (zh) | 2003-12-10 |
CN1313623C CN1313623C (zh) | 2007-05-02 |
Family
ID=29398523
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB031314732A Expired - Fee Related CN1313623C (zh) | 2002-05-15 | 2003-05-15 | 具有亲水和疏水区域的生物分子芯片平板制备方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US7794799B1 (zh) |
EP (1) | EP1364702A3 (zh) |
JP (1) | JP3828878B2 (zh) |
KR (1) | KR100455293B1 (zh) |
CN (1) | CN1313623C (zh) |
Cited By (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100424186C (zh) * | 2006-02-28 | 2008-10-08 | 宋家武 | 一种高灵敏度生物传感器基因芯片及临床诊断技术 |
CN1858593B (zh) * | 2006-03-23 | 2010-04-21 | 厦门大学 | 生物芯片专用亲疏水模式片基 |
CN1934447B (zh) * | 2004-03-17 | 2010-11-10 | 松下电器产业株式会社 | 生物芯片的制造方法 |
CN102016596A (zh) * | 2008-03-27 | 2011-04-13 | 哈佛学院院长等 | 纸基微流体系统 |
CN101221121B (zh) * | 2006-07-17 | 2011-08-17 | 三星电子株式会社 | 制造微阵列的方法 |
CN102246042A (zh) * | 2008-12-11 | 2011-11-16 | 皇家飞利浦电子股份有限公司 | 用于检测流体中的靶元素的感测器件 |
CN101263390B (zh) * | 2005-09-16 | 2011-11-16 | 株式会社山武 | 生物芯片用基板、生物芯片、生物芯片用基板的制造方法以及生物芯片的制造方法 |
CN102399290A (zh) * | 2011-11-04 | 2012-04-04 | 上海交通大学 | 一种在固体表面固定蛋白质的方法 |
CN101163638B (zh) * | 2004-12-23 | 2012-07-04 | 内诺克塞斯公司 | 微流装置及其用途 |
CN102614946A (zh) * | 2006-11-24 | 2012-08-01 | 新加坡科技研究局 | 用于处理液滴中样品的仪器及其使用方法 |
CN102748987A (zh) * | 2012-07-11 | 2012-10-24 | 北京工业大学 | 一种提高排水性能的换热器翅片 |
CN104357917A (zh) * | 2014-09-24 | 2015-02-18 | 中国科学院天津工业生物技术研究所 | 一种用于微阵列生物芯片的载体、其制备方法及微阵列生物芯片 |
US9557318B2 (en) | 2013-07-09 | 2017-01-31 | Curiox Biosystems Pte Ltd. | Array plates for washing samples |
CN107195764A (zh) * | 2017-06-27 | 2017-09-22 | 常州瑞丰特科技有限公司 | 匀光装置及其制备方法 |
US9874501B2 (en) | 2006-11-24 | 2018-01-23 | Curiox Biosystems Pte Ltd. | Use of chemically patterned substrate for liquid handling, chemical and biological reactions |
US9878328B2 (en) | 2010-07-23 | 2018-01-30 | Curiox Biosystems Pte Ltd. | Apparatus and method for multiple reactions in small volumes |
US9950323B2 (en) | 2012-02-05 | 2018-04-24 | Curiox Biosystems Pte Ltd. | Array plates and methods for making and using same |
CN108660068A (zh) * | 2018-02-13 | 2018-10-16 | 臻准生物科技(上海)有限公司 | 生物反应芯片及其制备方法 |
CN109313396A (zh) * | 2016-05-18 | 2019-02-05 | Illumina公司 | 使用图案化疏水性表面进行的自组装图案化 |
CN109759151A (zh) * | 2019-01-30 | 2019-05-17 | 浙江工业大学 | 一种基于条状的梯度阵列与楔形流道构成的自驱动纸基微流控芯片 |
US10545139B2 (en) | 2015-06-16 | 2020-01-28 | Curiox Biosystems Pte Ltd. | Methods and devices for performing biological assays using magnetic components |
CN111266142A (zh) * | 2020-03-19 | 2020-06-12 | 京东方科技集团股份有限公司 | 一种检测芯片、其修饰方法及反应系统 |
US10725020B2 (en) | 2007-11-14 | 2020-07-28 | Curiox Biosystems Pte Ltd. | High throughput miniaturized assay system and methods |
WO2020199016A1 (zh) * | 2019-03-29 | 2020-10-08 | 京东方科技集团股份有限公司 | 检测芯片及其使用方法、反应系统 |
CN113655053A (zh) * | 2021-08-09 | 2021-11-16 | 立讯电子科技(昆山)有限公司 | 一种比色杯及其制备方法 |
CN113716876A (zh) * | 2021-09-01 | 2021-11-30 | 电子科技大学 | 一种具有调控玻璃模糊度的智能玻璃制备方法 |
CN114153013A (zh) * | 2020-09-07 | 2022-03-08 | 合肥工业大学 | 一种微透镜阵列的制备方法及微透镜阵列 |
CN114308158A (zh) * | 2021-12-30 | 2022-04-12 | 广东昭宇生物科技有限公司 | 一种具备菌群平衡与修复功能的生物酶芯片的制备方法 |
CN115595579A (zh) * | 2022-10-31 | 2023-01-13 | 中国地质大学(北京)(Cn) | 发动机前压缩叶片表面疏水防冰涂层及其制备方法和应用 |
US11607682B2 (en) | 2019-01-15 | 2023-03-21 | Beijing Boe Technology Development Co., Ltd. | Detection chip, using method for the same, and reaction system |
US11692162B2 (en) | 2017-04-05 | 2023-07-04 | Curiox Biosystems Pte Ltd. | Methods, devices, and apparatus for washing samples on array plates |
CN116377759A (zh) * | 2023-03-23 | 2023-07-04 | 因达孚先进材料(苏州)股份有限公司 | 一种燃料电池用亲水-疏水碳纸的制备方法 |
WO2023130839A1 (zh) * | 2022-01-10 | 2023-07-13 | 成都齐碳科技有限公司 | 成膜支架、生物芯片、装置、制备方法及其应用 |
Families Citing this family (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040152083A1 (en) * | 2003-01-31 | 2004-08-05 | Leproust Eric M. | Multiple arrays with surface energy transition to maintain separation of samples on the arrays |
US20050064482A1 (en) * | 2003-08-27 | 2005-03-24 | Norihisa Mino | Microchip, process of manufacturing the same, and analytical method using the same |
JP4505287B2 (ja) * | 2003-08-27 | 2010-07-21 | パナソニック株式会社 | マイクロチップ並びにその製造方法及びそれを用いた検査方法 |
JP3949118B2 (ja) * | 2004-03-12 | 2007-07-25 | ジーエルサイエンス株式会社 | マイクロチップ |
US20050233366A1 (en) * | 2004-04-16 | 2005-10-20 | Norihisa Mino | Sample-analyzing device and process for manufacturing the same |
FR2871150B1 (fr) * | 2004-06-04 | 2006-09-22 | Univ Lille Sciences Tech | Dispositif de manipulation de gouttes destine a l'analyse biochimique, procede de fabrication du dispositif, et systeme d'analyse microfluidique |
KR100667298B1 (ko) * | 2005-01-10 | 2007-01-12 | 삼성전자주식회사 | 생분자 칩 및 그의 제조 방법 |
US7619215B2 (en) | 2005-02-07 | 2009-11-17 | Yangsun Kim | Sample plate for MALDI mass spectrometry and process for manufacture of the same |
KR100544860B1 (ko) * | 2005-02-07 | 2006-01-24 | (주)프로테오니크 | 시료 플레이트 및 이의 제조방법 |
GB2465906A (en) * | 2005-08-17 | 2010-06-09 | Waters Investments Ltd | Device for performing ionization desorption |
WO2007080761A1 (ja) | 2006-01-10 | 2007-07-19 | Murata Manufacturing Co., Ltd. | プローブアレイ基体及びその製造方法、プローブアレイの製造方法 |
US20070161119A1 (en) * | 2006-01-12 | 2007-07-12 | Peck Bill J | Methods for fabricating chemical arrays |
EP1832874B1 (de) * | 2006-03-07 | 2009-06-03 | Micronas Holding GmbH | Trägeroberfläche mit hydrophoben und hydrophilen Regionen |
WO2007123495A1 (en) * | 2006-04-25 | 2007-11-01 | National University Of Singapore | Method of patterning and product(s) obtained therefrom |
ES2291124B1 (es) * | 2006-07-28 | 2008-12-16 | Universidad Del Pais Vasco | Procedimiento para el tratamiento de superficies de soportes solidos. |
DE102006051482A1 (de) * | 2006-07-31 | 2008-02-14 | Nikolaus Bartels | Anordnung zum Erfassen von Substanzen, Herstellung der Anordnung und ihre Verwendung |
KR100755672B1 (ko) * | 2006-08-24 | 2007-09-05 | 삼성전자주식회사 | 기판 내에 형성된 프로브 셀 액티브를 포함하는 올리고머프로브 어레이 및 그 제조 방법 |
DE602007012282D1 (de) | 2006-10-12 | 2011-03-10 | Massachusetts Inst Technology | Multi-well-mikromusterung durch ablation |
KR100834745B1 (ko) | 2006-12-20 | 2008-06-09 | 삼성전자주식회사 | 분석 친화적 레이아웃에 기반한 올리고머 프로브 어레이칩, 이의 제조에 사용되는 마스크 및 이의 혼성화 분석방법 |
JP4904559B2 (ja) * | 2007-01-11 | 2012-03-28 | 大学共同利用機関法人情報・システム研究機構 | コーティング基板の製造方法、前記方法により製造されるコーティング基板、および、その用途 |
KR100819006B1 (ko) | 2007-02-13 | 2008-04-03 | 삼성전자주식회사 | 마이크로 어레이용 마스크 세트, 이의 제조 방법, 및마스크 세트를 이용한 마이크로 어레이의 제조 방법 |
KR100903969B1 (ko) | 2007-06-12 | 2009-06-25 | 삼성전자주식회사 | 마이크로 어레이, 마이크로 어레이용 기판 및 이들의 제조방법 |
WO2008157640A2 (en) | 2007-06-18 | 2008-12-24 | Illumina, Inc. | Microfabrication methods for the optimal patterning of substrates |
GR1006042B (el) * | 2007-06-20 | 2008-09-03 | Εθνικο Κεντρο Ερευνας Φυσικων Επιστημων (Ε.Κ.Ε.Φ.Ε.)-Δημοκριτος | Μεθοδος για την κατασκευη μικροσυστοιχιας |
KR100858722B1 (ko) * | 2007-08-16 | 2008-09-17 | 한국생산기술연구원 | 소수성 박막의 잉크젯 패터닝방법 |
KR100891097B1 (ko) * | 2007-08-27 | 2009-03-31 | 삼성전자주식회사 | 바이오칩 및 그 제조 방법 |
JP5182292B2 (ja) | 2007-11-22 | 2013-04-17 | 株式会社村田製作所 | プローブアレイ用基体ならびにプローブアレイおよびその製造方法 |
KR100961282B1 (ko) * | 2008-03-14 | 2010-06-03 | 포항공과대학교 산학협력단 | 친수성 표면과 소수성 표면을 갖는 멤브레인의 제조방법 |
FR2929864B1 (fr) * | 2008-04-09 | 2020-02-07 | Commissariat A L'energie Atomique | Auto-assemblage de puces sur un substrat |
KR101042106B1 (ko) * | 2008-11-06 | 2011-06-16 | 서울대학교산학협력단 | 액적 충돌을 이용한 마이크로액체 패터닝 방법 |
US8784673B2 (en) * | 2008-11-14 | 2014-07-22 | Northeastern University | Highly organized single-walled carbon nanotube networks and method of making using template guided fluidic assembly |
KR101144064B1 (ko) * | 2009-12-09 | 2012-05-23 | (주)유 바이오메드 | 마이크로어레이 칩 및 그의 제조방법 |
DE102009059112A1 (de) * | 2009-12-18 | 2011-06-22 | Biotype Diagnostic GmbH, 01109 | Eine Vorrichtung zur Bestimmung molekularer Wechselwirkungen, sowie eine Folie zur Herstellung einer solchen |
KR101347854B1 (ko) * | 2010-02-19 | 2014-01-07 | 한국과학기술원 | 표면에너지 차이를 이용한 바이오칩 제작방법 |
JP5593736B2 (ja) | 2010-03-02 | 2014-09-24 | セイコーエプソン株式会社 | 造形方法及び造形装置 |
KR101324199B1 (ko) * | 2010-09-16 | 2013-11-06 | 한국과학기술원 | 혼합된 자기조립 단분자 막을 이용한 단백질 결합 방법 및 그 방법을 이용한 단백질 칩 |
JP5757515B2 (ja) * | 2010-10-15 | 2015-07-29 | 学校法人立命館 | 撥水層を有する液滴保持ツールの製造方法 |
JP5548925B2 (ja) * | 2010-10-15 | 2014-07-16 | 学校法人立命館 | 液滴保持ツールの製造方法 |
PT105960A (pt) * | 2010-12-07 | 2012-08-16 | Ass For The Advancement Of Tissue Engineering Cell Based Technologies And Therapies A4Tec Associacao | Processo para deposição de biomateriais em substratos repelentes a água e resultantes biomateriais |
US20120156767A1 (en) * | 2010-12-17 | 2012-06-21 | Stmicroelectronics S.R.L. | Pcr device |
BR112013022889B8 (pt) | 2011-03-08 | 2022-12-20 | Univ Laval | Dispositivo centrípeto fluídico para testar componentes de um material biológico em um fluido, aparelho de teste e método de teste usando tal dispositivo centrípeto fluídico |
KR101925344B1 (ko) * | 2012-05-10 | 2018-12-05 | 리쿠아비스타 비.브이. | 전기 습윤 표시장치 |
KR101977413B1 (ko) * | 2012-06-14 | 2019-05-10 | 리쿠아비스타 비.브이. | 전기 습윤 표시 장치 및 이의 제조 방법 |
EP2684601B1 (en) * | 2012-07-13 | 2019-11-20 | Karlsruher Institut für Technologie | Formation of droplet or hydrogel arrays using hydrophilic-hydrophobic patterned surfaces for high-throughput screening applications |
KR101368998B1 (ko) * | 2012-08-07 | 2014-03-06 | 삼성테크윈 주식회사 | 표면 처리를 통한 회로 기판에서의 선택적 절연성 물질 충진 방법 |
CN103055982A (zh) * | 2012-12-31 | 2013-04-24 | 苏州汶颢芯片科技有限公司 | 一种微滴流动可控的微流控芯片及其制备方法 |
KR101589203B1 (ko) * | 2013-04-25 | 2016-01-28 | 한국과학기술원 | 초소수성 영역과 친수성 영역을 가지는 표면체의 제조방법 및 제조장치 |
CN104338333A (zh) * | 2014-05-28 | 2015-02-11 | 中国科学院力学研究所 | 一种空间水基液滴定位基片及其制备方法 |
USD799715S1 (en) | 2015-10-23 | 2017-10-10 | Gene POC, Inc. | Fluidic centripetal device |
US9872399B1 (en) * | 2016-07-22 | 2018-01-16 | International Business Machines Corporation | Implementing backdrilling elimination utilizing anti-electroplate coating |
WO2018131731A1 (ko) * | 2017-01-12 | 2018-07-19 | 한밭대학교 산학협력단 | 액상 시료를 나노 단위로 분배하는 기구 |
FR3063832B1 (fr) * | 2017-03-08 | 2019-03-22 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Procede d'auto-assemblage de composants microelectroniques |
EP3415230A1 (en) * | 2017-06-16 | 2018-12-19 | Danmarks Tekniske Universitet | Regulation of droplet size on an element post fabrication |
TW202100247A (zh) | 2019-01-29 | 2021-01-01 | 美商伊路米納有限公司 | 流通槽 |
JP7228129B2 (ja) * | 2019-03-28 | 2023-02-24 | 株式会社豊田中央研究所 | レーザー脱離/イオン化質量分析用の有機シリカ基板、及び、それを用いたレーザー脱離/イオン化質量分析法 |
CN112386399B (zh) * | 2019-08-12 | 2023-05-09 | 湖南早晨纳米机器人有限公司 | 一种纳米手术机器人以及制作方法 |
AU2022232933A1 (en) | 2021-03-11 | 2023-09-07 | Nautilus Subsidiary, Inc. | Systems and methods for biomolecule retention |
CN113385393B (zh) * | 2021-05-31 | 2022-12-27 | 中物院成都科学技术发展中心 | 一种仿沙漠甲虫结构复合材料及其制备方法 |
KR20230000037A (ko) * | 2021-06-23 | 2023-01-02 | 삼성디스플레이 주식회사 | 표시 장치 및 그의 제조 방법 |
CN113713868B (zh) * | 2021-09-13 | 2023-05-12 | 北京京东方技术开发有限公司 | 一种微流控制芯片及其制作方法 |
WO2023244832A1 (en) * | 2022-06-17 | 2023-12-21 | Saudi Arabian Oil Company | Manufacturing mixed wettability surfaces |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6026432B2 (ja) * | 1977-11-24 | 1985-06-24 | 三井東圧化学株式会社 | 塗料組成物 |
US5079600A (en) * | 1987-03-06 | 1992-01-07 | Schnur Joel M | High resolution patterning on solid substrates |
JP2606900B2 (ja) * | 1988-09-08 | 1997-05-07 | 株式会社東芝 | パターン形成方法 |
US5063081A (en) * | 1988-11-14 | 1991-11-05 | I-Stat Corporation | Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor |
US6589726B1 (en) * | 1991-09-04 | 2003-07-08 | Metrigen, Inc. | Method and apparatus for in situ synthesis on a solid support |
US5474796A (en) * | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
US6121048A (en) * | 1994-10-18 | 2000-09-19 | Zaffaroni; Alejandro C. | Method of conducting a plurality of reactions |
US5688642A (en) * | 1994-12-01 | 1997-11-18 | The United States Of America As Represented By The Secretary Of The Navy | Selective attachment of nucleic acid molecules to patterned self-assembled surfaces |
US5702754A (en) * | 1995-02-22 | 1997-12-30 | Meadox Medicals, Inc. | Method of providing a substrate with a hydrophilic coating and substrates, particularly medical devices, provided with such coatings |
US6207369B1 (en) * | 1995-03-10 | 2001-03-27 | Meso Scale Technologies, Llc | Multi-array, multi-specific electrochemiluminescence testing |
US6130098A (en) * | 1995-09-15 | 2000-10-10 | The Regents Of The University Of Michigan | Moving microdroplets |
CA2260807C (en) | 1996-07-18 | 2006-03-28 | Basf Aktiengesellschaft | Solid supports for analytical measuring processes, a process for their preparation, and their use |
DE19628928A1 (de) * | 1996-07-18 | 1998-01-22 | Basf Ag | Feste Träger für analytische Meßverfahren, ein Verfahren zu ihrer Herstellung sowie ihre Verwendung |
US5958345A (en) * | 1997-03-14 | 1999-09-28 | Moxtek, Inc. | Thin film sample support |
US6008892A (en) * | 1997-05-23 | 1999-12-28 | Molecular Dynamics, Inc. | Optical substrate for enhanced detectability of fluorescence |
EP0895083B1 (en) * | 1997-08-01 | 2009-09-23 | Canon Kabushiki Kaisha | Reaction site array, preparation of it, reaction process using it and quantitative determination method of substance in sample solution using it |
JP4313861B2 (ja) * | 1997-08-01 | 2009-08-12 | キヤノン株式会社 | プローブアレイの製造方法 |
DE19754978C2 (de) * | 1997-12-11 | 2000-07-13 | Bruker Daltonik Gmbh | Probenträger für die MALDI-Massenspektrometrie nebst Verfahren zur Herstellung der Platten und zum Aufbringen der Proben |
CN1109109C (zh) * | 1999-09-20 | 2003-05-21 | 中国科学院力学研究所 | 多元蛋白芯片及其制法和用途 |
KR100618804B1 (ko) * | 2000-04-18 | 2006-08-31 | 삼성전자주식회사 | 소수성화 처리를 이용한 선택적 원자층 증착막 형성방법 |
WO2001098222A1 (en) * | 2000-06-20 | 2001-12-27 | Kabushiki Kaisha Toshiba | Transparent film-coated substrate, coating liquid for transparent film formation, and display device |
JP3632837B2 (ja) * | 2000-10-31 | 2005-03-23 | 住友ベークライト株式会社 | 金属ベースメラミン樹脂化粧板 |
US6833542B2 (en) * | 2000-11-13 | 2004-12-21 | Genoptix, Inc. | Method for sorting particles |
KR100429910B1 (ko) * | 2001-09-12 | 2004-05-03 | 학교법인 포항공과대학교 | 저에너지 전자빔을 이용하는 고정밀 패턴 형성 방법 |
CN1156700C (zh) * | 2001-10-30 | 2004-07-07 | 东南大学 | 在线单生物分子检测芯片的制作方法 |
US7007710B2 (en) * | 2003-04-21 | 2006-03-07 | Predicant Biosciences, Inc. | Microfluidic devices and methods |
-
2002
- 2002-05-15 KR KR10-2002-0026730A patent/KR100455293B1/ko not_active IP Right Cessation
-
2003
- 2003-05-09 EP EP03252923A patent/EP1364702A3/en not_active Withdrawn
- 2003-05-15 US US10/438,334 patent/US7794799B1/en not_active Expired - Fee Related
- 2003-05-15 JP JP2003136789A patent/JP3828878B2/ja not_active Expired - Fee Related
- 2003-05-15 CN CNB031314732A patent/CN1313623C/zh not_active Expired - Fee Related
Cited By (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1934447B (zh) * | 2004-03-17 | 2010-11-10 | 松下电器产业株式会社 | 生物芯片的制造方法 |
CN101163638B (zh) * | 2004-12-23 | 2012-07-04 | 内诺克塞斯公司 | 微流装置及其用途 |
CN101263390B (zh) * | 2005-09-16 | 2011-11-16 | 株式会社山武 | 生物芯片用基板、生物芯片、生物芯片用基板的制造方法以及生物芯片的制造方法 |
CN100424186C (zh) * | 2006-02-28 | 2008-10-08 | 宋家武 | 一种高灵敏度生物传感器基因芯片及临床诊断技术 |
CN1858593B (zh) * | 2006-03-23 | 2010-04-21 | 厦门大学 | 生物芯片专用亲疏水模式片基 |
CN101221121B (zh) * | 2006-07-17 | 2011-08-17 | 三星电子株式会社 | 制造微阵列的方法 |
CN102614946A (zh) * | 2006-11-24 | 2012-08-01 | 新加坡科技研究局 | 用于处理液滴中样品的仪器及其使用方法 |
US9581527B2 (en) | 2006-11-24 | 2017-02-28 | Agency For Science, Technology And Research | Apparatus for processing a sample in a liquid droplet and method of using the same |
US9874501B2 (en) | 2006-11-24 | 2018-01-23 | Curiox Biosystems Pte Ltd. | Use of chemically patterned substrate for liquid handling, chemical and biological reactions |
US10725020B2 (en) | 2007-11-14 | 2020-07-28 | Curiox Biosystems Pte Ltd. | High throughput miniaturized assay system and methods |
CN102016596A (zh) * | 2008-03-27 | 2011-04-13 | 哈佛学院院长等 | 纸基微流体系统 |
CN102016596B (zh) * | 2008-03-27 | 2014-09-17 | 哈佛学院院长等 | 纸基微流体系统 |
CN102246042A (zh) * | 2008-12-11 | 2011-11-16 | 皇家飞利浦电子股份有限公司 | 用于检测流体中的靶元素的感测器件 |
CN102246042B (zh) * | 2008-12-11 | 2015-04-29 | 皇家飞利浦电子股份有限公司 | 用于检测流体中的靶元素的感测器件 |
US9878328B2 (en) | 2010-07-23 | 2018-01-30 | Curiox Biosystems Pte Ltd. | Apparatus and method for multiple reactions in small volumes |
US10632468B2 (en) | 2010-07-23 | 2020-04-28 | Curiox Biosystems Pte Ltd. | Apparatus and method for multiple reactions in small volumes |
CN102399290A (zh) * | 2011-11-04 | 2012-04-04 | 上海交通大学 | 一种在固体表面固定蛋白质的方法 |
US9950323B2 (en) | 2012-02-05 | 2018-04-24 | Curiox Biosystems Pte Ltd. | Array plates and methods for making and using same |
US10792661B2 (en) | 2012-02-05 | 2020-10-06 | Curiox Biosystems Pte Ltd. | Array plates and methods for making and using same |
CN102748987A (zh) * | 2012-07-11 | 2012-10-24 | 北京工业大学 | 一种提高排水性能的换热器翅片 |
US9557318B2 (en) | 2013-07-09 | 2017-01-31 | Curiox Biosystems Pte Ltd. | Array plates for washing samples |
CN104357917A (zh) * | 2014-09-24 | 2015-02-18 | 中国科学院天津工业生物技术研究所 | 一种用于微阵列生物芯片的载体、其制备方法及微阵列生物芯片 |
US10545139B2 (en) | 2015-06-16 | 2020-01-28 | Curiox Biosystems Pte Ltd. | Methods and devices for performing biological assays using magnetic components |
CN109313396A (zh) * | 2016-05-18 | 2019-02-05 | Illumina公司 | 使用图案化疏水性表面进行的自组装图案化 |
US11692162B2 (en) | 2017-04-05 | 2023-07-04 | Curiox Biosystems Pte Ltd. | Methods, devices, and apparatus for washing samples on array plates |
CN107195764A (zh) * | 2017-06-27 | 2017-09-22 | 常州瑞丰特科技有限公司 | 匀光装置及其制备方法 |
CN108660068A (zh) * | 2018-02-13 | 2018-10-16 | 臻准生物科技(上海)有限公司 | 生物反应芯片及其制备方法 |
CN108660068B (zh) * | 2018-02-13 | 2022-04-05 | 臻准生物工程(山西)有限公司 | 生物反应芯片及其制备方法 |
US11607682B2 (en) | 2019-01-15 | 2023-03-21 | Beijing Boe Technology Development Co., Ltd. | Detection chip, using method for the same, and reaction system |
CN109759151A (zh) * | 2019-01-30 | 2019-05-17 | 浙江工业大学 | 一种基于条状的梯度阵列与楔形流道构成的自驱动纸基微流控芯片 |
WO2020199016A1 (zh) * | 2019-03-29 | 2020-10-08 | 京东方科技集团股份有限公司 | 检测芯片及其使用方法、反应系统 |
US11654435B2 (en) | 2019-03-29 | 2023-05-23 | Boe Technology Group Co., Ltd. | Detection chip, method for operating detection chip, and reaction system |
CN111266142A (zh) * | 2020-03-19 | 2020-06-12 | 京东方科技集团股份有限公司 | 一种检测芯片、其修饰方法及反应系统 |
CN114153013A (zh) * | 2020-09-07 | 2022-03-08 | 合肥工业大学 | 一种微透镜阵列的制备方法及微透镜阵列 |
CN113655053A (zh) * | 2021-08-09 | 2021-11-16 | 立讯电子科技(昆山)有限公司 | 一种比色杯及其制备方法 |
CN113716876A (zh) * | 2021-09-01 | 2021-11-30 | 电子科技大学 | 一种具有调控玻璃模糊度的智能玻璃制备方法 |
CN114308158A (zh) * | 2021-12-30 | 2022-04-12 | 广东昭宇生物科技有限公司 | 一种具备菌群平衡与修复功能的生物酶芯片的制备方法 |
WO2023130839A1 (zh) * | 2022-01-10 | 2023-07-13 | 成都齐碳科技有限公司 | 成膜支架、生物芯片、装置、制备方法及其应用 |
CN115595579A (zh) * | 2022-10-31 | 2023-01-13 | 中国地质大学(北京)(Cn) | 发动机前压缩叶片表面疏水防冰涂层及其制备方法和应用 |
CN116377759A (zh) * | 2023-03-23 | 2023-07-04 | 因达孚先进材料(苏州)股份有限公司 | 一种燃料电池用亲水-疏水碳纸的制备方法 |
CN116377759B (zh) * | 2023-03-23 | 2023-12-08 | 因达孚先进材料(苏州)股份有限公司 | 一种燃料电池用亲水-疏水碳纸的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
EP1364702A2 (en) | 2003-11-26 |
EP1364702A3 (en) | 2004-05-06 |
KR20030088782A (ko) | 2003-11-20 |
JP3828878B2 (ja) | 2006-10-04 |
CN1313623C (zh) | 2007-05-02 |
JP2004004076A (ja) | 2004-01-08 |
US7794799B1 (en) | 2010-09-14 |
KR100455293B1 (ko) | 2004-11-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1313623C (zh) | 具有亲水和疏水区域的生物分子芯片平板制备方法 | |
US20210086174A1 (en) | Flow cells with hydrogel coating | |
US7790350B2 (en) | Method and materials for patterning a neutral surface | |
CN1916767A (zh) | 光刻图形的形成方法 | |
JP7123928B2 (ja) | 樹脂膜とパターン化ポリマー層を含むアレイ | |
WO2016126882A1 (en) | Methods and devices for de novo oligonucleic acid assembly | |
CN1684902A (zh) | 贴花转印微制造 | |
WO2010026944A1 (ja) | 高分子膜および積層体 | |
CN1909977A (zh) | 微电子衬底的湿法蚀刻处理用旋涂保护涂层 | |
CN101061432A (zh) | 印花转印刻蚀 | |
US20130323652A1 (en) | Method of fabricating patterned functional substrates | |
US7994097B2 (en) | Microarray, substrate for microarray and methods of fabricating the same | |
EP4221883A1 (en) | Methods for making flow cells | |
CN117642225A (zh) | 流通池及其制备方法 | |
US8871423B2 (en) | Photoresist composition for fabricating probe array, method of fabricating probe array using the photoresist composition, composition for photosensitive type developed bottom anti-reflective coating, fabricating method of patterns using the same and fabricating method of semiconductor device using the same | |
CN117460574A (zh) | 流通池及其制备方法 | |
KR100791335B1 (ko) | 마이크로 어레이 및 이의 제조 방법 | |
CN117836054A (zh) | 流通池及其制备方法 | |
CN117858756A (zh) | 流通池及其制备方法 | |
KR100843147B1 (ko) | 올리고머 프로브 어레이용 기판과 올리고머 프로브 어레이및 이들의 제조 방법 | |
KR100891098B1 (ko) | 바이오칩 및 그 제조 방법 | |
JP2005206454A (ja) | 結晶化用基板及びその製造方法 | |
WO2023180161A2 (en) | Methods for making flow cell surfaces | |
JP2005521556A (ja) | 高い拡散率の浸透剤を用いての膜の性能を向上させるプロセス | |
EP4214506A1 (en) | Nanopatterned films with patterned surface chemistry |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C17 | Cessation of patent right | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070502 Termination date: 20140515 |